Angiopoietin 2 Mediates the Differentiation and Migration of Neural Progenitor Cells in the Subventricular Zone after Stroke

摘要: Ischemic stroke stimulates neurogenesis in the adult rodent brain. The molecules underlying stroke-induced have not been fully investigated. Using real-time reverse transcription-PCR, we found that substantially up-regulated angiopoietin 2 (ANG2), a proangiogenic gene, expression subventricular zone neural progenitor cells. Incubation of cells with recombinant human ANG2 significantly increased number β-III tubulin-positive cells, marker immature neurons, but did alter glial fibrillary acidic protein (GFAP)-positive astrocytes, suggesting promotes neuronal differentiation. Blockage receptor, Tie2, small interference RNA (siRNA)-Tie2 attenuated (rhANG2)-increased tubulin mRNA levels compared transfected control siRNA. Chromatin immunoprecipitation analysis revealed CCAAT/enhancer-binding (C/EBPβ) by rhANG2 bound to tubulin, which is consistent published data there are several C/EBPβ binding sites promoter gene. In addition, enhanced migration measured single neurosphere assay. Tie2 siRNA-Tie2 and Tie2-neutralizing antibody suppress ANG2-enhanced migration. However, inhibition matrix metalloproteinases GM6001 blocked Collectively, our suggest interaction ANG2, factor, its receptor cell differentiation into lineage whereas regulates through metalloproteinases, do require Tie2.